Abstract The proposal is an early phase clinical trial with application of advanced magnetic resonance imaging (MRI) techniques to an increasingly common clinical dilemma faced in managing papillary micro carcinoma (PMC) patients. Over the past 25 years, there has been a six-fold increase in the incidence of thyroid cancer in the United States. Since the mid-1990s, a sharp rise in incidence led to the recognition that thyroid cancer had become a major public health problem, and it continues to be one. At least half of the rapid increase in the incidence of thyroid cancer is due to PMC, which has a recurrence rate of up to 6% and a disease-specific survival rate of more than 99% following surgical resection. The need for immediate surgical treatment has been brought into question by two recent prospective clinical studies that demonstrated that even without any treatment, the vast majority of these PMCs remains stable in size and confined to the thyroid gland when followed with active surveillance for up to 10 years. The failure to accurately predict the aggressiveness of tumors pre-operatively often leads to immediate surgical resection in nearly all patients with PMC, exposing a huge number of people with indolent malignancies to the risks of surgery. Non-invasive MRI metrics have shown promise in differentiating benign and malignant thyroid nodules but so far, have not been able to stratify thyroid tumors based on aggressiveness before surgery. We will aim to address this clinical challenge by evaluating diffusion weighted (DW-)MRI and dynamic contrast enhanced (DCE-)MRI methods that provide quantitative biomarkers incorporating integrated information on tumor cellularity and vascularity. The goal of this pilot clinical trial is to lay the groundwork to critically evaluate and compare MRI biomarkers as quantitative (surrogate) biomarkers of aggressiveness in PMCs and to provide the scientific basis for their translation into patient management. Metrics from data modeling will accurately quantify tumor cellularity, vascularity and their associated heterogeneity and improve assessment of tumor aggressiveness in PMC. The long-term goal of this work will be to perform clinical trials using individualized biomarkers to provide a personalized management approach that recommends either immediate surgery or active surveillance for PMC patients. The hypothesis is that (i) systematic evaluation of a reliable and reproducible protocol for the acquisition and processing of MRI data will improve the accuracy of DW-MRI and DCE-MRI to quantify tumor cellularity, vascularity and their associated heterogeneity. (ii) MRI biomarkers will identify PMCs with aggressive phenotypes that should be candidates for immediate surgery rather than active surveillance. The specific aims of the study are: Specific Aim 1: To evaluate a reproducible and reliable DW-MRI and DCE-MRI protocol for PMC. Specific Aim 2: To identify quantitative MRI biomarkers that can predict PMCs with aggressive histologic and molecular phenotypes.